Dabigatran Etexilate Mesylate (VII), chemically known as β-Alanine, N-[[2-[[[4-[[[(hexyloxy) carbonyl] amino] iminomethyl] phenyl] amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-, ethyl ester, methanesulfonate, is a thrombin inhibitor. The structure of Dabigatran Etexilate in the form of mesylate salt is as shown below in compound of formula (VII):

The compound of formula VII above also represents Dabigatran Etexilate (Wherein MsOH is absent in formula VII).
Dabigatran etexilate was first described in International patent application WO 98/37075 and the process for manufacture was reported in WO 2006/000353 and also in J. Med. Chem, 2002, 45, 1757 by N. Hauel et al.
Two general routes have been reported for the synthesis of Dabigatran etexilate (VII). The first process was disclosed in WO98/37075 and a modification of the first route has been described in WO 2006/000353. Both the synthetic routes start from the 3-nitro-4-methylamino-benzoic acid and are presented in Scheme 1.

Both the routes (Scheme-1) involved three common intermediates II, III and VI, of which VI can be obtained from either IV or V depending on the substituted glycine used for the synthesis. According to the previous reports, all the intermediates required column purification to prepare substantially pure Dabigatran Etexilate and the processes are not suitable for industrial scale production of the same. The synthesis of intermediate II has been reported in several patents and require either a chromatographic purification or a tedious purification procedure such as converting into the HCl salt followed by recrystallization to obtain 97% pure intermediate II. In both cases, the yield is less than 50%. Similarly, Intermediate III is one of the key intermediates in the Dabigatran Etexilate synthesis and the process involves the reduction of nitro group either by hydrogenation in presence of Pd/C or in presence of sodium dithionite. Both the methods (Scheme-1, catalyst Pd/C) resulted in the formation of product with higher level of impurities. WO 2012/004397 reports the product as a solid and in US 20110082299 (WO 2009/111997) wherein the reduction of nitro group is performed in presence of Sodium dithionite, the intermediate is reported as a dark red coloured viscous liquid and used without further purification. However, it is essential that the key intermediate III must be very pure to obtain the intermediate VI as very pure compound thereby isolating the Dabigatran Etexilate API with required purity in the final stage.
Similarly, the intermediates IV and V prepared by either CDI or PPA mediated coupling with glycine derivatives followed by acetic acid mediated cyclization resulted in the formation of highly impure products, and purified by either column chromatography or by converting the crude reaction mixture to suitable salts. Both the methods afforded low yield and purity thereby the process is not suitable for the commercial scale production of Dabigatran Etexilate.